Find out below about the projects and activities that Neuromod+ has funded.
Feasibility Study Calls
Call 1 - March 2023
Dario Farina, Alejandro Pascual Valdunciel – Imperial College London
Anna Latorre, Kailash Bhatia – University College London
Tremor is a motor disorder which can severely affect the quality of life of patients, leading to significant socio-economic impact. In this project we aim to explore a non-invasive and cost-effective solution for mitigating tremor. Particularly, we will investigate the effectiveness of transcutaneous spinal cord stimulation (tSCS) in treating tremor and how this technique interferes with motor control. tSCS involves weak currents delivered through electrodes attached to the skin. It has been proven to modulate the central nervous system and based on our previous research on nerve stimulation, we assume that it could potentially disrupt the tremorgenic oscillations at the spinal cord, preventing them to reach the muscles. We will explore the tremor reduction efficacy and safety of tSCS in Essential Tremor and attempt to characterize the neuromodulatory effects on motor control of different stimulation parameters, including a closed-loop stimulation strategy synced with the tremor.
Paul Briley, Richard Morriss – University of Nottingham
Sudheer Lankappa – University of Plymouth
Peter Liddle – University of Oxford
Transcranial magnetic stimulation (TMS) is approved by NICE for the treatment of depression. Clinical TMS uses magnetic pulses to modify activity of frontal brain regions. The amount of benefit that patients get from TMS is variable. We are developing an approach for boosting the effects of TMS by delivering it in synchrony with another neuromodulation technique called transcranial alternating current stimulation (tACS). We are commencing a study of tACS-synchronised TMS (“tsTMS”) in people with depression to understand how the two techniques work together. We are requesting funds to purchase a device for non-invasively monitoring activity within frontal cortex. This device, called “functional near infrared spectroscopy” (fNIRS), is quick to setup and can be used before, during, and after stimulation. This would allow us to study the extent, and region specificity, of tsTMS modulation of frontal cortical activity, beyond that of TMS alone, furthering the development of our approach.
Antonio Valentin – King’s College London
Tamar Makin – University College London
Tiago Da Silva Costa – Newcastle University
Kat Richardson – CloseNIT Network (Newcastle University)
Amparo Guemes – University of Cambridge
Active Patient and Public Involvement (PPI) is crucial to co-develop user-centred, ethically sound and sustainable neurotechnologies, whilst promoting transparency, accountability and inclusivity. We aim to establish a structured approach to PPI in the development and use of neurotechnologies in the UK, by setting clear principles, guidelines and tools for co-production by stakeholders including patients, clinicians, researchers, regulators, and the public. As a first step, we will host a workshop that celebrates successful PPI initiatives. We will first hear from patients, clinicians, researchers, and regulators about their effective PPI implementation methods. Next, we will discuss the practical steps for establishing PPI. Beyond the networking opportunities, deliverables include the consolidation, in a workshop white paper, of the best existing guidelines, policies, and online resources to support effective PPI strategies. This will form the basis for establishing the first set of guidelines and tools for PPI in neurotechnologies design in the UK.
JeYoung Jung (University of Nottingham), Marcus Kaiser (University of Nottingham), Matthew Lambon Ralph (University of Cambridge), Elena Stylianopoulou (University of Cardiff)
Dementia affects millions globally and the loss of neurotransmitters is a hallmark of dementia. Decreased excitatory (glutamate) and inhibitory (GABA) neurotransmitters have been linked to cognitive and behavioural symptoms in dementia. Focused ultrasound stimulation modulates neural activity by affecting cell membrane features. Unlike other techniques, FUS has high spatial resolution and can stimulate deep-brain structures involved in dementia. This proposal suggests using FUS combined with neuroimaging for developing personalized dementia treatment. The proposal aims to explore and validate the efficacy of FUS in modulating neurotransmitter systems to improve human memory. It involves investigating neurochemical mechanisms of FUS effects, predicting outcomes based on individual neural characteristics, and developing evidence-based FUS protocols to improve memory. The proposal contributes to understanding FUS effects on memory and potentially lead to new treatments for dementia.
Miriam Klein-Flugge, Lilian Weber, Johannes Algermissen – University of Oxford
Elsa Fouragnan, Siti Yakuub – University of Plymouth
We aim to further improve iTBS for depression by optimizing the TMS pulse shape. Overcoming the engineering limitations of conventional devices, our novel TMS device can deliver monophasic iTBS. Compared to conventional biphasic, monophasic iTBS induces stronger brain plasticity – key to the antidepressant effects.
Here we will test the hypothesis that monophasic iTBS will reverse cognitive deficits in depression more effectively than conventional biphasic. We will use tasks we have shown to be sensitive to depression and single-dose stimulation (Figure 1). Our project aims to establish proof-of-concept evidence to advance towards a next-step clinical trial.
Sophie Morse, Simon Schultz, James Choi, Ann Go – Imperial College London
Focused ultrasound is capable of non-invasive neuronal modulation. It can, with high spatial precision, reach deep brain structures normally accessible only through invasive deep brain stimulation. Producing both short and long-lasting changes in neuronal excitability and firing rates, focused ultrasound offers enormous potential as an investigative tool for neuroscience and as a treatment for neurological and psychiatric disorders. How ultrasound induces neuromodulation, however, needs to be better understood in order to develop more precise and effective protocols for the treatment of promising brain disorders. Three-photon microscopy can non-invasively perform deep-tissue, live-cell structural and functional imaging. With its ability to image structures such as the murine hippocampi without the need of a craniotomy, it is an ideal tool to better understand the mechanism of ultrasound neuromodulation. We here propose to build the first simultaneous ultrasound neuromodulation and three-photon imaging system to advance our mechanistic understanding and improve patient treatments.
Call 2 - November 2023
Rob Dineen, Stephen Jackson, Caroline Blanchard, Alex Turner – University of Nottingham
William Whitehouse – National Paediatric A-T Clinic, Nottingham University Hospitals NHS Trust
Ataxia telangiectasia (A-T) is an inherited cerebellar neurodegenerative disorder. People with A-T experience unwanted involuntary movements (e.g. dystonia, chorea, athetosis and tremors), interfering with daily tasks, social interactions and reducing quality-of-life. Pharmacological treatments are ineffective and limited by side effects.
Non-invasive Median Nerve Stimulation (MNS) suppresses involuntary movements in Tourette syndrome. Based on this, in 2023 we successfully undertook a pilot study (STIM-A-T) of MNS in 5 people with A-T, with video recording during motor tasks with MNS on and off. The video recordings have undergone expert rating for abnormal movements, but this is time-consuming and suffers subjective biases, hence not ideal for large-scale clinical trials.
To support a clinical trial of MNS in people with A-T (grant submission 2024-Q3/Q4), we will work collaboratively with computer scientists and clinical neurologists to develop AI-based quantitative video analysis providing unbiased measures of involuntary movements trained on labelled videos from people with A-T.
Marcus Kaiser, Mohammad Zia Katshu – University of Nottingham
James Choi, Sophie Morse – Imperial College London
Unlike other noninvasive brain stimulation techniques, focused ultrasound can safely reach deep-brain structures. It therefore competes with invasive deep-brain stimulation through implants. One challenge of the field is that stimulation is often inconsistent between participants or patients and that results in the same participant vary between sessions. This has led to the idea of closed-loop approaches which we have already tested in animal studies invasively showing a great increase in stimulation effectiveness (Zaaimi et al., Nature Biomedical Engineering, 2023). Here, we test closed-loop approaches in humans noninvasively, observing the effect of focused ultrasound stimulation. We will test whether closed-loop stimulation, either coupled to ongoing brain rhythms or to task execution, leads to more consistent and stronger changes in cognitive performance.
While we initially test our approaches in healthy participants, our aim is to provide pilot results for future study of interventions in patients.
Mahnaz Arvaneh, Daniel Blackburn – University of Sheffield
Lise Sproson – Sheffield Teaching Hospital NHS FT, NIHR Devices for Dignity Med Tech Cooperative
Ismail Yussuf – Israac Centre, Sheffield
Non-invasive neurotechnology like EEG and brain stimulation can revolutionize healthcare by providing accurate diagnoses and personalized treatments. However, it is crucial to consider the social and cultural implications to ensure inclusivity for historically marginalized groups. In the UK, African ethnic minority communities face health disparities and are often underrepresented in neurotechnology research. Barriers include limited awareness, cultural and language differences, mental health stigma, and design issues. For instance, African-style hair hampers EEG and electrical brain stimulation effectiveness, while wearing hijab poses religious concerns. To address these challenges, this project will investigate the acceptance and inclusivity of neurotechnology among people from Somali heritage. Collaborating with Israac, a Sheffield-based Somali Community association, this study will use user-centered approaches to evaluate existing technology, identify barriers, propose solutions for greater ethnic representation in neurotechnology research, and co-develop alternative designs for better acceptability and inclusivity.
Alekhya Mandali, James Alix – University of Sheffield
Motor neurone disease (MND) is a fatal condition that causes muscle weakness. During the disease, the brain becomes ‘overactive’ well before symptoms start and is critical to disease progression. Over the last 20 years, small electrical currents applied by electrodes on the scalp have been shown to alter the brain’s activity. Recent work shows that these weak currents can dampen down this ‘overactive’ brain, making this approach relevant for MND. A recent randomised-controlled trial using one stimulation form decreased this ‘overactivity’ in MND patients. However, the study was limited to one stimulation type, and it is unknown if other forms of stimulation work better.
This project will compare two stimulation types on healthy participants by measuring a criterion used to assess the brain’s overactivity in MND. The best stimulation will then be tested on a few MND patients. The study outcomes will enable future studies to treat MND using electrical currents.
Jacinta O’Shea, Tim Denison, Verena Sarrazin, Emile Radyte, Fatima Khokar – University of Oxford
Majid Memarian – Magstim Limited
Michael Browning – Oxford Health NHS Trust
Depression is the leading cause of adult disability worldwide. 1 in 3 patients do not respond to medications/psychotherapy. Transcranial Magnetic Stimulation (TMS) is a promising alternative. A rapid form (intermittent theta burst stimulation, iTBS) delivered in 3 minutes is as effective as conventional 37-minute treatment, and highly intensive multi-session iTBS greatly increases clinical effectiveness.
We aim to further improve iTBS for depression by optimizing the TMS pulse shape. Overcoming the engineering limitations of conventional devices, our novel TMS device can deliver monophasic iTBS. Compared to conventional biphasic, monophasic iTBS induces stronger brain plasticity – key to the antidepressant effects.
Here we will test the hypothesis that monophasic iTBS will reverse cognitive deficits in depression more effectively than conventional biphasic. We will use tasks we have shown to be sensitive to depression and single-dose stimulation (Figure 1). Our project aims to establish proof-of-concept evidence to advance towards a next-step clinical trial.
Simon Schultz, Hayriye Cagnan – Imperial College London
Ashwini Oswal, David Dupret – University of Oxford
Memory disorders are a key component of neurodegenerative disease, and can have a debilitating effect on quality of life. Attempts to alleviate symptoms and enhance memory function using drug-based approaches have had very limited success. In this project we will demonstrate proof of principle for a new approach for enhancing memory performance, which will work by non-invasively amplifying the sharp-wave ripple (SWR) signal that coordinates the transfer of information from the hippocampus into the neocortex in memory consolidation. The project will involve addressing two current hurdles to realising this technology: (i) demonstration of proof of principle in a rodent model, and (ii) non-invasive detection of SWRs in human subjects using magnetoencephalography. Addressing these gaps in the literature will enable follow-on work integrating these techniques with focused ultrasound neurostimulation, in order to treat memory impairment in patients suffering from neurodegenerative disorders.
Tracy Farr, Marcus Kaiser, Anna Lion – University of Nottingham
Tim England – Royal Derby Hospital
Many neurological diseases, for example stroke, have very few effective treatments. This represents a significant burden to the individual and society, therefore, novel therapies are required. Low intensity focussed ultrasound stimulation is an emerging neuromodulation technique that can stimulate various pathways with greater accuracy, penetration and potentially fewer side effects compared to conventional neurostimulation methods. Before moving the technology into clinical trials, it is necessary to improve our understanding of the mechanisms by which the stimulation can alter brain function. We aim to develop flexible transducers, focussing devices, and equipment for mechanistic driven research in animal models. This will also facilitate testing of optimal dosing regimens and windows that will inform the design of future clinical studies and could ultimately lead to options for therapies that would benefit patient populations.
Call 3 - May 2024
Mahnaz Arvaneh, Daniel Blackburn – University of Sheffield
Lise Sproson – Sheffield Teaching Hospital NHS FT, NIHR Devices for Dignity Med Tech Cooperative
Ismail Yussuf – Israac Centre, Sheffield
To foster acceptance and inclusivity of non-invasive neurotechnology in African ethnic minority communities, we plan to co-create videos featuring interviews with end users and clinicians. This video will highlight the benefits and address the unique needs and concerns of these communities. Through personal stories and expert insights, we aim to build trust and demonstrate the positive impact of neurotechnology on health and well-being, promoting its acceptance and inclusivity.
Elsa Fouragnan – University of Plymouth
Samuel Hughes – University of Exeter
Chronic pain affects one in five individuals, and for a third of these, current analgesics offer little relief, and alternative treatments are scarce. To innovate targeted treatments, mechanistic insight of discrete pain modulation circuits is required.
Several subdivisions of the dorsal anterior cingulate cortex (dACC), a deep cortical region, mediate pain processing via connections with other regions involved in pain perception and descending pain modulation systems in both the brainstem and spinal cord.
Our study capitalises on the response of brain cells to transcranial ultrasound stimulation (TUS) to precisely target multiple subsections of the dACC during experimentally induced pain, supported by pilot data. This method allows us to uncover intrinsic relationships between pain-related cortical activity and descending endogenous analgesic systems.
Employing a multimodal approach, we will integrate TUS–dACC with neuroimaging, neurophysiology, and psychophysical techniques. This pioneering research aims to pave the way for groundbreaking clinical applications in pain management.
Richard Morriss, Paul Briley – University of Nottingham
Anxiety disorders affect 301 million people worldwide. Relapse or resistance to psychotherapy and medications is common. Transcranial magnetic stimulation (TMS) is an approved neuromodulation treatment for mental health conditions. However, clinical response remains variable. Using additional neuromodulation techniques to boost the effects of TMS, such as transcranial alternating current stimulation (tACS), may improve its efficacy.
This project will investigate the mechanisms of action of simultaneous TMS and tACS, and its potential for treating anxiety symptoms. We will use electroencephalography (EEG) to personalise stimulation based on an individuals’ brain waves, and will examine brain activity and communication between brain areas to understand how such an approach works. We will use established markers of anti-anxiety effect to assess the treatment potential of the approach. We will share our anonymised data to support the development of dual neuromodulation protocols.
Katherine Dyke, Domenica Veniero – University of Nottingham
Luigi Tamè – University of Kent
Nicholas Holmes, University of Birmingham
Activity in the regions of the brain relating to movement and touch can be measured by applying stimulation to the wrist, and non-invasive magnetic stimulation to the head. These measures can improve understanding into what happens during neurological conditions, including Parkinson’s disease and dystonia. However, first, we need to know how well these approaches work in healthy adults of different ages. Specifically, we need more research into people over 35 years old, as these techniques are often based on work from younger adults. Our research collaboration will combine non-invasive brain stimulation and a brain imaging approach called ‘electroencephalography’ (EEG) to improve understanding of how the healthy brain ages. We will also create evidence-based guidelines for individualising stimulation parameters, allowing research groups to optimise measures for healthy and clinical groups. This new information will provide a unique and valuable reference for the assessment of clinical disorders of touch and movement.
Charlotte Stagg, Polytimi Frangou, Saad Jbabdi, William Clarke – University of Oxford
Elly Martin, Angelika Zarkali – UCL
One of the most important neurochemicals in the human brain is Acetylcholine (ACh). It is central in learning and attentional processes, and its deficit has been linked to neurodegenerative disorders including Alzheimer’s and Parkinson’s. Yet, our efforts to understand its exact role have been hindered by the lack of 1) non-invasive ways to measure ACh activity reliably in the human brain and 2) non-pharmacological and non-invasive ways to enhance ACh activity to reverse deficits.
Recent advances in neuroimaging and brain stimulation now allow us to develop tools to
overcome these challenges. Here, we will harness focused ultrasound neuromodulation to activate brain regions that are rich in ACh for the first time. We will use newly developed spectroscopic imaging tools to quantify how our intervention changes ACh in the brain. Our work will set the foundation for future investigations of ACh and for developing ACh-enhancing therapeutic interventions against cholinergic deficits.
Early Career Researcher Funding Calls
Call 1
Awardee: Justin Andrushko, Assistant Professor & Vice-Chancellor Fellow, Department of Sport, Exercise and Rehabilitation, Northumbria University.
Host PI: Charlotte Stagg, Nuffield Department of Clinical Neurosciences, Oxford University
Investigating the role of theta-gamma transcranial alternating current stimulation (tACS) on sensorimotor functional connectivity and inhibition using ultra-high field MRI.
Objectives:
- To gain practical and theoretical skills around transcranial alternating current stimulation (tACS) as a neuromodulation tool to modulate motor function from leading experts in the field.
- Develop a new academic collaboration and provide structured mentorship around neuroimaging skills (including but not limited to: bash scripting, brain imaging data structure [BIDS] formatting, structural and functional MRI preprocessing and analysis) to one of Professor Charlotte Stagg’s DPhil students.
Outcomes:
- During my two-week visit to the University of Oxford, I observed and assisted with multiple data collection sessions in a novel, cutting-edge, multimodal neuroimaging study. This study involves delivering tACS inside a 7-tesla magnetic resonance imaging (MRI) scanner and acquiring functional and spectroscopy data before, during, and after stimulation. I gained knowledge and experience around how to safely and effectively administer transcranial electrical stimulation protocols both in and out of an MRI scanner. This has been invaluable as I venture in to the world of non-invasive brain stimulation in my own lab at Northumbria University.
- I spent several hours each day working closely with the lead PhD student on the project. I used some of my previously-developed teaching materials around preprocessing and analysing structural and functional MRI data to deliver informal educational lectures on the various steps required to managed and process the data appropriately. Alongside teaching the theory of these steps, I assisted in the development of a series of eight new, flexible analysis pipelines (bash scripts) for each step of the analysis. Combined, these scripts create a complete, modular, end-to-end (pre)processing pipeline for beginner neuroimagers. These have significantly sped up the data analysis process for the student and has given her the confidence to continue working on the project independently. She has already successfully processed data for 16 participants (three sessions each, minimum 5 scans each ≈ 240 scans). We are in the process of making these scripts open access to promote open science and support novice neuroimagers. Going forward, to provide continued to support to the student and project, we have scheduled weekly conference calls.
- I also spent time piloting protocol setups and stimulation montages for a subsequent multi-investigator Neuromod+ grant application (already submitted) in collaboration with Professor Charlotte Stagg at the University of Oxford.
- I also gave a talk to the group at Oxford on cognitive-motor recovery post-stroke and gave demonstrations on various novel cognitive-motor training games I have written in Python for use in the newly submitted Neuromod+ grant.
- I also got involved in an additional research project involving KINARM robotic upper limb movement practice with simultaneous brain stimulation and recording with EEG and tACS.
Overall, this research visit has strengthened relationships and has set a solid foundation for many future collaborative research projects related to neuromodulation for motor performance and motor recovery in neurologically intact individuals and stroke survivors respectively.
Awardee: Runhao Lu, MRC Cognition and Brain Sciences Unit, University of Cambridge.
Host PI: Matthew Rushworth, Department of Experimental Psychology, Oxford University
Exploring Transcranial Focused Ultrasound Stimulation (FUS) in Cognitive Neuroscience
Objectives:
- To gain both theoretical and practical skills in transcranial focused ultrasound stimulation (FUS) within the domain of cognitive neuroscience.
- To build research collaborations with FUS researchers in Oxford.
Outcomes:
- During my visit to the University of Oxford, I acquired substantial practical and theoretical knowledge about the application of FUS in cognitive neuroscience. I worked under the guidance of Prof. Matthew Rushworth and collaborated closely with the lead PhD student, Deng Pan. The project that I involved builds on their previous work, which shows that the hippocampus is a key region for encoding abstract task structures. As a follow-up, this FUS study aims to investigate the causal role of the hippocampus in structure learning using the Brainbox NeuroFUS PRO 2.0 system.
- I actively observed and assisted in several sessions conducted for each participant. Before the FUS session, participants underwent MRI scanning to capture T1 structural and pseudo-CT images. Using these images, I learned to operate K-Plan, an advanced simulation and planning tool for transcranial ultrasound procedures. Under Deng’s guidance, I used K-Plan to determine optimal parameters such as focal point coordinates, skull thickness compensation, and transducer positioning, ensuring precise and safe stimulation delivery for each participant.
- Each FUS session spanned several hours and involved multiple stages. I assisted in preparation steps like degassing water, setting up the transducer, and preparing participants by gelling their hair. I applied my previous experience with TMS during the neuronavigation process, which allowed me to efficiently assist in accurate transducer placement. This hands-on experience deepened my understanding of the setup required for successful FUS application, particularly in ensuring correct positioning and optimal contact with the transducer.
- I also participated in the regular calibration of the FUS machine, which included calibrating power output and verifying accuracy using a sound level meter. These calibration steps are critical to ensure consistent and safe delivery of ultrasound energy, and this hands-on experience provided me with a comprehensive understanding of the operational aspects of FUS technology.
- Beyond the technical skills, I also attended group meetings/journal clubs in Oxford, where I engaged in discussions with researchers on FUS and other neuroscience methods. These interactions broadened my perspective on FUS applications and provided opportunities to exchange knowledge and establish potential collaborations with experts in the field.
Overall, this research visit has offered me hands-on experience in FUS and allowed me to establish a collaboration with leading FUS researchers in Oxford. Understanding the entire procedure and the associated challenges has strengthened my confidence in using this cutting-edge technology in the future.
Awardee: Bhushan Thakkar, Postdoctoral Research Fellow, Division of Population Health and Genomics, School of Medicine, University of Dundee.
Host PI: Thomas Graven-Nielsen, Center for Neuroplasticity and Pain (CNAP), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Denmark
Objectives:
- To foster new collaborative relationships between the University of Dundee and CNAP to optimise the use of brain stimulation techniques like TMS and tDCS
- to improve understanding of the neural mechanisms that can explain the outcomes of these brain stimulation techniques
- to improve technical knowledge in using EEG and tDCS to optimise and personalise the use of rTMS in people with NP and in healthy volunteers
Call 2
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Awardee: Mica Komarnyckyj, Neuroimaging Research Associate, Division of Psychology & Mental Health, University of Manchester.
Host PI: Elsa Fouragnan, Brain Research & Imaging Centre, University of Plymouth
Awardee: Alekhya Mandali, Lecturer, School of Psychology, University of Sheffield.
Objectives:
- TBC
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